The invention relates to methods for diagnosing and treating psychiatric disorders in a patient. In particular, the intention relates to methods for identifying genetic markers that are associated with treatment resistant psychiatric disorders and administering a treatment for the treatment resistant psychiatric disorder to the patient based on identifying the genetic markers. The genetic markers may include polymorphisms such as single nucleotide polymorphisms (SNPs) and the alternate treatment may include foregoing administering typical or atypical antipsychotic drugs (APDs), where the patient has been diagnosed with a treatment resistant psychiatric disorder, and instead administering a different treatment regimen or a new APD as disclosed herein.
Psychiatric disorders such as schizophrenia, bipolar disorder, and depression with psychotic features are estimated to affect millions or Americans. Many patients with psychiatric disorders are successfully treated with typical or atypical APDs. For example, following treatment with typical APDs (i.e., first generation APDs) or atypical APDs (i.e., second generation APDs), about 70% of people with schizophrenia have significant remission of positive symptoms.69 However, many patients with psychiatric disorders are resistant to treatment with typical or atypical APDs. For example, about 30% of people with schizophrenia are resistant to treatment with APDs, where treatment resistant schizophrenia (TRS) may be defined as presence of moderate to severe positive symptoms despite treatment with two or more trials of APDs other than clozapine at usually adequate doses for 4-6 weeks.6 Some population studies have suggested that an even higher proportion of treatment resistant (TR) patients exists.1-4 
Furthermore, treatment with certain APDs may have undesirable side effects. For example, olanzapine, clozapine, and quetiapine may cause an increased risk of developing metabolic abnormalities such as the impaired glucose metabolism/diabetes and weight gain/obesity.48 As such, if a patient has a treatment resistant psychiatric disorder, administering some APDs is not beneficial and may be detrimental. However, there currently are no available diagnostic tests for predicting whether a patient having a psychiatric disorder will be resistant to treatment with APDs. Here, genetic markers that are associated with treatment resistant psychiatric disorders are identified. By using these genetic markers, clinicians can stratify psychiatric patients based on the markers and provide a more personalized treatment for patients with treatment resistant psychiatric disorders and avoid administering typical or atypical APDs and instead administer a different treatment regimen or a new APD as disclosed herein.